Huntington's disease (HD) is an inherited, progressive neurodegenerative disorder characterized by chorea, movement dysfunction, cognitive impairment, and behavioral disturbances. Deficiencies in striatal (BDNF), which plays an important role in survival, growth, differentiation, and functioning of neurons, has been implicated in the pathogenesis of HD. Glatiramer acetate (Copaxone(R)) is a safe and well-tolerated, FDA-approved drug used for the treatment of multiple sclerosis. Glatiramer acetate has been shown to increase BDNF levels in immune cells, which may be partly related to its therapeutic benefit in multiple sclerosis. Our preliminary findings demonstrate that glatiramer acetate can elicit concentration-dependent increases in BDNF protein levels in both WT and HD STHdh striatal cells and in striatal neurons from HD N171-82Q transgenic mice, providing evidence that glatiramer acetate may also prove useful to treat HD. Thus, the goals of this exploratory R21 proposal are to test the ability of glatiramer acetate to delay or prevent disease phenotypes in HD transgenic and knock-in mice (Aim1); and to determine the effects of glatiramer acetate on BDNF and huntingtin expression levels in serum and in different brain regions of WT and HD mouse models at different doses (Aim 2). The repurposing of an FDA-approved drug, such as glatiramer acetate, into a new indication, i.e. HD, will facilitate a rapid path into a critical unmet medical need. The excellent safety and tolerability record of glatiramer acetate makes it an ideal candidate for drug repurposing efforts. The successful completion of these preclinical studies will provide the basis for a clinical trial testing glatiramer acetate in human HD patients.